In 1992, Fasciclin IV (latterly called G-Sema I) was cloned as one of the genes involved in guidance for neuron in grasshopper. The next year, the existence of a gene family of which members encode analogous domains and are distributed in a wide range of species covering insects, viruses, nematodes, and human was revealed, and the gene family members were designated “Semaphorin genes”. To date, more than ten genes belonging to the Semaphorin family have been reported (Cell, 81, 471-474 (1995)).
These Semaphorin genes characteristically contains, in the amino acid sequences which they encode, similar structures called semaphorin domain each consisting of about 500 amino acids (Neuron, 14, 941-948 (1995); Cell, 7, 1389-1399 (1993)). Although the homologies of the above amino acid sequences among Semaphorins are 80-20% and are thus not always high, some of the amino acid residues are extremely well conserved as exemplified by thirteen cysteine residues located at conserved positions. In the regions other than semaphorin domains, Semaphorins are highly varied one another. Specifically, Semaphorins include both of secretory and membrane-bound forms, and have various structures including those having Ig domains, thrombospondin domains, or a cluster of basic amino acids at its carboxy terminus.
Among such Semaphorins, functions have been verified for only a few, including, for example, Fasciclin IV of grasshopper, Semaphorins I and II of drosophila, Collapsin of chick, and Semaphorin III which corresponds to Collapsin in mammals. All of these Semaphorins are, however, known to inhibit axon outgrowth and synapsis formation during the stage of ontogenesis, that is, in the course of the neural network formation at the embryonic or fetal stage (Neuron, 14, 941-948 (1995); Neuron, 14, 949-959 (1995); Cell, 8, 631-639 (1995); Cell, 75, 1389-1399 (1993); Cell, 75, 217-227 (1993); and Neuron, 9, 831-845 (1992)).
Although Semaphorin genes are known to perform its function at the ontogenetic stage as described above, it has not yet been ascertained whether or not they perform any function also in the adult. However, some Semaphorin genes are known to be expressed also in the adult in which formation of the neural network has been already completed, suggesting that they may have some function also in said adult. For example, the central nervous system (CNS) in the adult is widely known to lack regenerating ability, and some Semaphorins which inhibit neurite outgrowth may conceivably function as a CNS-neuron regeneration inhibitor in the adult (Nature, 378, 439-440 (1995)). In addition, it has been suggested, by a recently reported study on Semaphorin III-knockout mouse, that a certain Semaphorin may probably act in inhibiting the growth of cardiac muscles (Nature, 383, 525-528 (1996)). Furthermore, a certain Semaphorin has been suggested to be involved in survival and aggregation of B lymphocytes (Proc. Natl. Acad. Sci. USA, 93, 11780-11785 (1996))
It is thus being demonstrated that Semaphorins play important roles not only in the nervous system but also in non-nervous systems, and therefor attracting great interest in studies on said Semaphorins.